Membrane binding proteins of coronaviruses

J Alsaadi, Entedar A; Jones, Ian M

By contrast with S, the CoV envelope protein (E) is a small hydrophobic integral membrane protein ranging from 76 to 109 amino acids. It has an N-terminal domain, a long α-helical transmembrane domain and a C-terminal hydrophilic domain and is found as a minor component in all CoV groups [41, 42] . The E protein is also palmitoylated at all three of its Cys residues [43] but the role of this secondary modification is debated. For MHV-CoV, single Cys residue changes do not significantly impair virus growth but modification of all three residues results in severe attenuation [44, 45] . For SARS-CoV; however, triple mutation of the conserved Cys' does not impact secretion of virus antigen from expressing cells suggesting no particular dependence on palmitoylation [46] . Two membrane topologies have been demonstrated for E protein, hairpin or transmembrane, and it has been suggested that the level of palmitoylation may moderate their relative proportion, in turn allowing modified membrane curvature [45, 47] . The E protein has demonstrated functions in virus assembly and release (below) and it appears to induce membrane curvature in the ERGIC leading to membrane scission of the budding virus particle and its release [48] . Envelope protein also interacts with the M protein and mutants of M that are unable to bud from cells can be complemented by mutated forms of E [49, 50] . The membrane curving properties of E are such that co-expression of M and E is adequate for the efficient formation of virus-like particles [48, 51] , which can also incorporate S if it is co-expressed [52] . For many CoVs, including MHV, E protein has also been shown to have a role as an ion channel, a viroporin [53, 54] . E function as a viroporin, including the trafficking of virions in the secretory pathways and membrane permeability, is essential for virus growth [55] . E also interacts with host cellular proteins including Proteins Associated with Lin Seven 1 (PALS1), which is known to maintain the epithelial cell junction, with clear implications for the virus assembly site in the Golgi [56, 57] . While E function is critical for virus assembly, its viroporin activity in mobilizing calcium ions and its interactions with host tight junction cell proteins has been also implicated as a mediator of pathology in some CoV infections [55, 57] .